Histologic image of oral squamous cell carcinoma (hematoxylin-eosin stain, original magnification  20). The degree of keratini- zation (blue arrows), nuclear pleomorphism (orange arrowheads), mitosis (black arrowheads), invasion, and reaction of surrounding tissues were evaluated. Troeltzsch et al. Clinicopathologic Features of OSCC in Different Age Groups. J Oral Maxillofac Surg 2014. 

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... relevant variables were recorded from a review of the medical records. The variable ' 'age' ' was categorized as previously suggested 5,6,8,10,12,15,[32][33][34] and defined as the predictor variable. The following outcome variables were recorded: patient age at the first OSCC diagnosis, tumor anatomic site, risk factor exposure, preoperative imaging details, underlying systemic diseases, surgical details, type of reconstruction, air- way management, healing process and postoperative complications, hospitalization duration, and survival time. Pathologic stage and grade were expressed using the TNM system according to the guidelines of the American Joint Committee on Cancer (AJCC). Analysis of the hematoxylin-eosin-stained pathologic spec- imens followed predefined and validated protocols (Fig 1). 36 All specimens were tested for p16 INK4a overex- pression, which was used as a surrogate marker for HPV infection, as recommended by other investigators. 1,27,37 Examination of the specimens for p16 overexpression was performed in tissue microarray blocks. A prepared immunohistochemistry kit using a murine monoclonal antibody was used for p16 INK4a testing (CINtec, Ventana Medical Systems, Illkirch, France). As suggested by Duncan et al, 37 only specimens with very strong (3+) staining for p16 INK4a were considered HPV positive (Figs 2A-C). An HPV association with OSCC was defined as the binary primary out- come ...

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... cell carcinoma of the head and neck (HNSCC) is among the most common malignancy worldwide, with a peak incidence between the fifth and seventh 1-3 decade of life. Recent data have indicated the increasing importance of HNSCC in young and very 3-10 elderly adults. The exact definitions for young and 10-15 very elderly oncology patients have been provided. The incidence of HNSCC in young patients has been 10,11,15,16 increasing, and the increased life expectancy necessitates consideration of curative treatment of 4,17,18 HNSCC in very elderly patients. It is common knowledge that long-term exposure to the classic risk factors such as alcohol consumption, smoking, and betel nut chewing has been strongly associated with 11,12,15,16,19,20 the etiology of HNSCC. Although these factors can be involved in HNSCC development in 3,10,11 young and very elderly adults, the rather early or late incidence of the disease in these age groups suggests additional conditions such as chronic inflammation, genetic alterations, and viral infection 20-23 that might predispose these patients to HNSCC. In particular, in young, nonsmoking patients with HNSCC, a viral component in carcinogenesis, namely, an infection with human papillomavirus (HPV), has 8,21,24 been discussed. Studies have indicated a caus- ative role of HPV infection in oropharyngeal SCC, especially base of the tongue and tonsillar 25-27 malignancies. The role of HPV in the development of oral SCC (OSCC) in patients of all age groups is 2,7,22,28-30 under scientific debate. Because of the transient nature of HPV infection, the failure of HPV detection in HNSCC specimens might not always 31 imply tumorigenesis without HPV involvement. Although the clinicopathologic parameters of HNSCC in young and very elderly patients have been reported 3,5,6,10,11,15,16,32-34 in isolation by several investigators, comparative studies of HNSCC in these age groups 3,12,15 have been scarce. The purpose of the present study was to examine whether differences in the clinical and pathologic pa- 10-12,15 rameters of OSCC in predefined age groups exist. We hypothesized that the clinicopathologic features of OSCC would vary at different ages and that HPV infection plays a crucial role in carcinogenesis, especially in young and very elderly patients. The specific aims of the present study were to analyze OSCC cases available retrospectively in a large population, to allocate these cases to predefined age groups, and to compare the clinical, pathologic, and therapeutic parameters of OSCCs among the age groups. The conduct of the study was in accordance with ethical requirements, internal review board approval was obtained, and the international guidelines for re- 35 porting clinical trials were followed. To address the research purpose, we designed and implemented a retrospective cohort design. The study population included all patients presenting to the oral and maxillofacial surgery department (Ludwig-Maximilians-University, Munich, Germany) for evaluation and management of the primary manifestation of OSCC from 2001 to 2012. Patients who presented for management of recurrent disease and those who had undergone preceding radiotherapy or chemo- therapy were excluded from the present review. The patients’ age at the first OSCC diagnosis determined their allocation into groups. The age limits were set 5,6,8,10,12,15,32-34 as recommended previously. Patients younger than 40 years old were considered young patients and those older than 80 years were considered very elderly patients. A group of patients aged 40 to 80 years was randomly chosen from all other eligible probands and considered middle-aged patients. The randomized choice of the middle-aged patients was rendered by using the random number generation function of Microsoft Excel (Microsoft Office 2011, Redmond, WA). The size of the middle- age group was limited to prevent skewness. The relevant variables were recorded from a review of the medical records. The variable ‘age’ was categorized 5,6,8,10,12,15,32-34 as previously suggested and defined as the predictor variable. The following outcome variables were recorded: patient age at the first OSCC diagnosis, tumor anatomic site, risk factor exposure, preoperative imaging details, underlying systemic diseases, surgical details, type of reconstruction, airway management, healing process and postoperative complications, hospitalization duration, and survival time. Pathologic stage and grade were expressed using the TNM system according to the guidelines of the American Joint Committee on Cancer (AJCC). Analysis of the hematoxylin-eosin–stained pathologic specimens followed predefined and validated protocols 36 INK4a (Fig 1). All specimens were tested for p16 overexpression, which was used as a surrogate marker for HPV 1,27,37 infection, as recommended by other investigators. Examination of the specimens for p16 overexpression was performed in tissue microarray blocks. A prepared immunohistochemistry kit using a murine INK4a monoclonal antibody was used for p16 testing (CINtec, Ventana Medical Systems, Illkirch, France). As 37 suggested by Duncan et al, only specimens with INK4a very strong (3+) staining for p16 were considered HPV positive (Figs 2A-C). An HPV association with OSCC was defined as the binary primary outcome variable. Statistical analysis of the extracted data was performed using statistical software (SPSS for Windows, release 17.0, Chicago, IL). With respect to the variable scale, the c 2 test, Student’s t test, and analysis of variance (ANOVA) were used. Pearson’s correlation coefficients were computed, where appropriate. The significance level was set at P .05. A retrospective analysis of the patient files generated 739 cases that met the initial inclusion criteria and qual- ified for additional review. After reviewing the medical records with respect to the preset age limits, 11 patients (1.4%) were assigned to the young patient group and 17 (2.3%) to the very elderly patient group. For correct statistical analysis, the middle-aged group was adjusted in size, as previously explained, and 17 patients were included. The mean age of the entire sample was 60.8 Æ 20.26 years (male patients, 61.46 Æ 19.67; female patients, 59.71 Æ 21.78). The mean age was 34.2 Æ 2.8, 55.7 Æ 8.17, and 83.1 Æ 1.18 years in the young, middle-aged, and very elderly patient groups, respec- tively. In all groups, a slight male predominance was found, with a 1.2:1 ratio in the young group, 2.4:1 in the middle-aged group, and 1.8:1 in the very elderly group. One patient in the young group was pregnant at the diagnosis of primary OSCC. The oral tongue was the predilection site of OSCC in the young patients, the alveolar process was mostly affected in the elderly patients, and the floor of the mouth was in the middle-aged patients. These findings were statistically significant ( P < .01, c 2 test). We found it remarkable that most of our patients with OSCC at a young or advanced age did not display the classic risk factors, such as alcohol consumption, smoking, or betel nut chewing. In contrast, all the patients in the middle-aged group admitted frequent and extensive consumption of alcohol or tobacco, or both. These differences were statistically significant ( P < .01, c 2 test). The pathologic characteristics, such as tumor extent, neck node involvement, resection margins, and OSCC grade, did not differ significantly among the age groups. Most of the patients in these cohorts had AJCC stage II and III disease, with a tendency toward more limited disease at younger ages. The distribution among the age groups seemed to be equal. The tumor extent, neck node involvement, and OSCC grade in the young patient group did not differ significantly from those in the other groups. The presence of HPV was diagnosed in about 20% of the cancer cases and was equally distributed among the age groups. The age-adjusted demographic and clinicopathologic parameters of OSCC are summarized in Table 1. The presence of congestive heart disease, arterial occlusive disease, metabolic disorders, and hyperten- sion impaired the general health of the very elderly patients significantly more often than in the other patient groups ( P < .01, c 2 test). Primary defect closure after surgical tumor removal was the preferred therapeutic approach in the young patient and very elderly patient groups. Microvascular flaps were used in 1 patient in each group. The microvascular flap in the young patient was a radial forearm flap. A scapular osteomyocutanous flap was used in a very elderly patient. Radical surgery and elaborate reconstruction with microvascular flaps were more commonly applied in the middle-aged group ( P < .007, c 2 test). Soft tissue resection defect closure was achieved with radial forearm flaps in 6 cases and an anterolateral thigh flap in 1; bony reconstruction was rendered with a fibular graft in 1 patient and a microvascular hip graft in 2. Overall, 10 patients (58.8%) underwent microvascular reconstruction in the middle-aged group. Postoperative surgery-related complications, such as postoperative bleeding, airway obstruction, or wound dehiscence, were rare, and their occurrence was distributed equally among the age groups. The hospitalization duration differed significantly among the age groups ( P < .001, ANOVA). The relevant clinical and therapeutic parameters are listed in Table 2. Cancer-related death occurred in 41% of the very elderly patients after a mean follow-up period of 27.3 Æ 3.8 months. Only 2 cases of cancer-related death were noted in the very elderly group after a mean survival period of 42.3 Æ 7.43 months. No tumor- ...

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... stage and grade were expressed using the TNM system according to the guidelines of the American Joint Committee on Cancer (AJCC). Analysis of the hematoxylin-eosin-stained pathologic spec- imens followed predefined and validated protocols (Fig 1). 36 All specimens were tested for p16 INK4a overex- pression, which was used as a surrogate marker for HPV infection, as recommended by other investigators. ...